Inhaltsübersicht

Inhaltsübersicht

1. Introduction
2. Scope
3. References
4. Definitions
5. Abbreviations
6. General principles of clinical evaluation
6.1 What is clinical evaluation?
6.2. When is clinical evaluation undertaken and why is it important?
6.3 How is a clinical evaluation performed?
6.4 Who should perform the clinical evaluation?
7. Definition of the scope of the clinical evaluation (Stage 0)
8. Identification of pertinent data (Stage 1)
8.1 Data generated and held by the manufacturer
8.2 Data retrieved from literature
9. Appraisal of pertinent data (Stage 2)
9.1 General considerations
9.2 The appraisal plan
9.3 Conduct of the appraisal
10. Analysis of the clinical data (Stage 3)
10.1 General considerations
10.2 Specific considerations
10.3 Where demonstration of conformity based on clinical data is not deemed appropriate
11. The clinical evaluation report (CER, Stage 4)
12. The role of the notified body in the assessment of clinical evaluation reports

Anhänge

A1 Demonstration of equivalence
A2 When should additional clinical investigations be carried out?
A3 Device description – typical contents
A4 Sources of literature
A5 Literature search and literature review protocol, key elements
A5.1 Background to the literature search and the literature review
A5.2 Objective
A5.3 Methods
A6 Appraisal of clinical data – examples of studies that lack scientific validity for demonstration of adequate clinical performance and/or clinical safety
A7 Analysis of the clinical data – compliance to specific Essential Requirements
A7.1 Conformity assessment with requirement on safety (MDD ER1 / AIMDD ER1)
A7.2 Conformity Conformity assessment with requirement on acceptable benefit/risk profile (MDD ER1 / AIMDD ER1)
A7.3 Conformity assessment with requirement on performance (MDD ER3 / AIMDD ER2)
A7.4 Conformity assessment with requirement on acceptability of undesirable side-effects (MDD ER6 / AIMDD ER5)
A8 Devices for unmet medical needs – aspects to consider
A9 Clinical evaluation report – proposed table of contents, examples of contents
A10 Proposed checklist for the release of the clinical evaluation report
A11 Information on declarations of interests
A12 Activities of notified bodies
A12.1 Notified body assessment of clinical evaluation by conformity assessment route
A12.2 Examination of a design dossier (Annex II.4; Annex 2.4) or of a type examination dossier (Annex III; Annex 3)
A12.3 Evaluation as part of quality system related procedures
A12.4 Notified body specific procedures and expertise

A5. Literature search and literature review protocol, key elements

 

The output of the literature search and literature review are:

  • Literature on the device in question and the equivalent device.
    Note: If the manufacturer holds own clinical data for the device in question (e.g. own pre- market clinical investigations, PMCF Studies, other PMS data), the literature is considered together with those data for consistent appraisal and overall analysis.
  • A review of the current knowledge/ the state of the art needed for the proper conduct of the appraisal and analysis of the clinical data of the device under evaluation and the equivalent device (i.e. applicable standards and guidance documents, information on the medical conditions that are relevant to the clinical evaluation, therapeutic/ management/ diagnostic options available for the intended patient population, etc.).

The literature collected may relate directly to the device in question (e.g. publications of clinical investigations of the device in question that have been performed by third parties, its side effects or complications, incidence reports) and/or to equivalent device, benchmark devices, other devices and medical alternatives available to the intended patient population.

The literature search and literature review protocol should address the background to and the objective of the review, specifying the literature review questions and the methods for identification, selection, collection and appraisal of the relevant publications needed to address them. It should include the literature search methodology (literature search protocol).

The selection of literature should be objective and justified, i.e. include all relevant data, both favourable and unfavourable. With respect to the clinical evaluation, it is important that the clinical evaluators are able to assess the degree to which the selected papers reflect the intended application/ use of the device.

Objective, non-biased, systematic search and review methods should be used. Examples are:

  • PICO (patient characteristics, type of intervention17, control, and outcome queries)
  • Cochrane Handbook for Systematic Reviews of Interventions
  • PRISMA (The Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement
  • MOOSE Proposal (Meta-analysis Of Observational Studies in Epidemiology)

The protocol should specify the elements described below, addressing the background, objective, and methods for identification, selection, and collection of the relevant publications to address the literature review questions.

A5.1. Background to the literature search and the literature review

This section documents the importance of and rationale for the literature review and includes, but is not limited to:

  • Device name/model
  • Importance of literature review to risk management process. The literature review will provide data on current interventions18 for the intended patient population (state of the art) in order to give input to the assessments of acceptable benefit/risk profiles, what is currently considered as providing a high level of protection of health and safety and what are considered acceptable side-effects.
  • Previous literature reviews
  • Importance of review to risk management process
  • Previous literature searches conducted by the manufacturer
  • If including equivalent or benchmark devices, name and model of the devices.
  • The CER will need to establish equivalence to the device under evaluation or the relevance of benchmark devices to the clinical evaluation.

A5.2. Objective

This section documents the research question(s), which should be consistent with the scope of the clinical evaluation and carefully constructed using a process (e.g. PICO):

  • Population(s)/disease(s) or condition(s)
  • Intervention(s)
  • Comparator group(s)/control(s)
  • Outcome(s)/endpoint(s)

The inputs for the review question(s) (e.g. PICO) are the device description and the intended performance of the device including any claims on clinical performance and clinical safety which the manufacturer wants to use. Also information from the risk management process is needed as an input.

A5.3. Methods

The methods section of the protocol documents the plans for literature search, study selection, data collection, and analysis methods. It defines the literature search strategy and the inclusion/exclusion criteria for the documents found.

The protocol should include:

  • the literature search methodology
    The purpose of a literature search protocol is to plan the search before execution. It should be developed and executed by persons with expertise in information retrieval, having due regard to the scope of the clinical evaluation set out by the manufacturer. The involvement of information retrieval experts will help to optimize literature retrieval to identify all relevant published literature.
    The importance of a literature search protocol is for critical appraisal of the methods. The search strategy should be based on carefully constructed review questions.
  • the sources of data that will be used and a justification for their choice (see Appendix A4, Sources of literature)
  • the extent of any searches of scientific literature databases (the database search strategy);
  • attempts to identify all published literature
  • which electronic databases are to be searched, with justification
  • the extent of any Internet searching and searching non-published information, including the search strategy and justification
  • exact search terms and any limits
  • limits for start and end dates of each search
  • the selection/criteria (such as inclusion/exclusion criteria) to be applied to published literature and justification for their choice
  • strategies for addressing the potential for duplication of data across multiple publications;
  • strategies for avoiding retrieving publications of data generated and already held by the manufacturer
  • the data collection plan that defines data management practices to ensure data integrity during extraction (e.g. quality control/second review of extracted data by additional reviewer)
  • the appraisal plan, which defines the methods for appraising each publication, including the relevance of the data to the intended clinical use and the methodological quality of the data
  • the analysis plan, which defines the methods for analysing the data including data processing and transformation

Any deviations from the literature search protocol should be noted in the literature search report.

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